OBJECTIVES: To estimate the effects of the apolipoprotein E (APOE)-É4 allele on the development of dementia and to elucidate its usefulness in the risk prediction of dementia in Japanese. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, in Japan. PARTICIPANTS: Five hundred twenty-three participants with deoxyribonucleic acid samples from a population of 1,073 community-dwelling participants without dementia aged 60 to 79. MEASUREMENTS: The risk estimates of the APOE-É4 allele on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: During 17 years of follow-up, 136 participants developed dementia, 81 of whom had AD and 39 VaD. After adjusting for age, sex, education, smoking, alcohol intake, systolic blood pressure, use of antihypertensive agents, glycosylated hemoglobin, serum total cholesterol, body mass index, and regular exercise, the risks of all-cause dementia and AD were significantly higher in APOE-É4 carriers than in noncarriers, but no such association was observed for VaD (all-cause dementia: hazard ratio (HR)=1.81, P=.004; AD: HR=3.42, P<.001; VaD: HR=1.08, P=.86). The area under the receiver operating characteristic curve was significantly greater when the APOE genotype was incorporated into a model with potential risk factors for AD (0.74 vs 0.68, P=.02). Other measures of model discrimination (net reclassification improvement: 0.18, P=.01; integrated discrimination improvement: 6.25, P<.001) also confirmed this improvement in AD risk assessment. CONCLUSION: The APOE-É4 allele is a risk factor for AD in the Japanese population. Information on APOE genotype improves AD risk assessment substantially beyond a model based on potential risk factors.
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